Search Results (79)

The diversity and abundance of the brain virome is an active field of investigation. However, how the brain virome relates to the presence of viruses outside of the nervous system remains unclear. The rationale for this study is that analyses across multiple biologically linked compartments within the same individuals provide an important opportunity to evaluate virome discordance and viral burden. To characterize viral prevalence and burden across anatomical compartments, we applied the targeted viral enrichment method ViroFind to matched postmortem brain (n = 66), cerebrospinal fluid (CSF; n = 24), and peripheral samples (spleen, peripheral blood mononuclear cells, and lymph nodes; n = 66) from individuals with and without human immunodeficiency virus (HIV) infection and substance use disorder (SUD) in the National NeuroAIDS Tissue Consortium. We detected nucleic acids from 27 viruses representing 12 taxa. Several viruses, including adenovirus, torque teno virus, Epstein–Barr virus, human herpesvirus 6 and 7, cytomegalovirus, parvovirus, and JC polyomavirus, showed significant inter-compartment differences in prevalence or burden. CSF exhibited lower overall viral diversity than brain or peripheral samples, whereas peripheral samples showed the highest viral burden. CNS viral detection was more likely when the same virus was also detected in the periphery. We also detected HBV and HCV in CNS samples despite them not being classically regarded as neurotropic. Broader virome profiling showed greater peripheral viral burden and diversity in HIV-positive than HIV-negative individuals, whereas SUD was not associated with overall viral burden differences. These findings highlight important cross-compartment differences in viral detection, including occurrence of occult HBV infection within the CNS, and support the value of CNS–periphery comparisons in virome studies. These findings can contribute to improved diagnosis and management of viral infections. Full article

Human Herpesvirus 6 (HHV-6) is a neurotropic virus associated with lifelong latency and stress-induced reactivation. Its role in major depressive disorder (MDD) remains unclear. This study investigated the association between HHV-6 infection and MDD and evaluated interaction effects with psychosocial and clinical factors. A cross-sectional study was conducted among 2403 university students in Thailand, including 52 participants with physician-diagnosed MDD and 2351 healthy controls. HHV-6 DNA was detected by quantitative polymerase chain reaction (qPCR) using saliva. Logistic regression and interaction analyses were performed. HHV-6 DNA was detected in 50.7% of participants. HHV-6 infection was not significantly associated with MDD (OR = 1.335, 95% CI: 0.766–2.328, p = 0.309). Multivariable analysis identified congenital disease, high-fat food consumption, stress, and depressive symptoms as independent predictors of MDD. Significant interaction effects were observed between HHV-6 and several factors. HHV-6 was not independently associated with MDD; however, exploratory interaction analyses identified potential relationships with selected psychosocial and host-related factors that require further validation. Full article

Background/Objectives: Long COVID-19 (LC-19), also known as Post-Acute COVID-19 Syndrome (PACS), is a chronic condition some people experience after an initial SARS-CoV-2 infection. The etiology of this complex, multifactorial disease remains largely unknown, although various theories have been propounded. This study aims to profile and compare the metabolic activity of cells of normal and LC-19 patients. Methods: A cohort of 20 individuals, 10 with LC-19 and 10 without LC-19, was selected based on their post-COVID-19 symptomatology. Saliva was tested for opportunistic viruses like Epstein–Barr virus (EBV) and Human Herpesvirus 6 (HHV-6). Lymphoblastoid cell lines derived from blood were analyzed using the Biolog Phenotype Mammalian Microarrays (PM-M1, PM-M6, and PM-M7) to assess metabolic activity across a wide array of growth substrates and effector molecules. Results: Unique metabolic profiles emerged across the controls and LC-19 groups. The SARS-CoV-2 infection causes an over two-fold enhanced utilization of glycolytic and anaerobic substrates and a reduced response to growth factors and effectors. The increased energy source utilization assessed in PM-M1 is unsustainable, and the LC-19 groups demonstrate this with a clear correlation with the number of LC-19 symptoms, demonstrating a trend consistent with metabolic reprogramming. The infection also results in a reduced response to growth factors and effectors, assessed in PM-M6 and PM-M7, with the level of reduction commensurate with the symptom burden. Conclusions: The data from the patient groups were analyzed and compared to construct a metabolic profile unique to individuals who developed LC-19, which could, in the future, be used for diagnosis and to identify targets for therapeutic intervention. Our study identified an LC-19-specific metabolic profile indicative of adaptive responses to stress, cellular dysfunction, and prolonged inflammation, leading to the reprogramming of bioenergetic pathways. Full article

Background and Clinical Significance: Human Herpesvirus 8-associated multicentric Castleman disease is a rare, lymphoproliferative disorder characterized by recurrent episodes of systemic inflammation. The disease is predominantly observed in human immunodeficiency virus-positive patients, but there is evidence of its occurrence in negative individuals. Its pathogenesis is driven by dysregulated cytokine activity, particularly interleukin 6. Additionally, these individuals have an increased risk of developing Kaposi Sarcoma, which may present simultaneously. Case Presentation: The current paper presents a case of a 58-year-old male patient admitted to the Hematology Department of the Emergency City Hospital in Timisoara, Romania, in October 2024, accusing fever, night sweats, palpitations, weight loss and general deterioration, approximately three months prior, with gradual progression. Clinical examination revealed bilateral lymphadenopathy in the cervical and inguinal regions. No cutaneous lesions were observed initially. Laboratory tests showed elevated inflammatory markers, pancytopenia, hypergammaglobulinemia and hyponatremia. HIV serology had negative results. CT imaging revealed extensive lymphadenopathy and splenomegaly. Further excisional biopsy of the inguinal and cervical lymphadenopathies was performed. Following the microscopic examination, the final diagnosis of Human Herpesvirus 8-associated multicentric Castleman disease concurrent with Kaposi Sarcoma was established. Conclusions: Human Herpesvirus 8-associated multicentric Castleman disease is predominantly observed in HIV-positive patients, but there is evidence of its occurrence in human immunodeficiency virus-negative individuals, presenting distinct epidemiological and pathological characteristics. Early and precise diagnosis is essential, as the disease can progress rapidly and may lead to severe or fatal outcomes. Full article

Human herpesvirus 6 (HHV-6) typically remains latent but can reactivate during immunosuppression caused by chemotherapy, potentially driving immune dysregulation. The NLRP3 inflammasome is a critical innate immune complex mediating pro-inflammatory signaling implicated in tumor progression and treatment toxicity. This study investigated the association between HHV-6 antigenemia and NLRP3 inflammasome activation in 193 chemotherapy-treated cancer patients at the Oncology Hospital in Al-Najaf, Iraq. Serological markers for HHV-6 IgG, IgM, and circulating viral antigen, along with serum NLRP3 levels, were quantified using ELISA. Active HHV-6 antigenemia was observed in over half the cohort, with 56.5% positive for IgM and 42.5% exhibiting antigenemia. Elevated serum NLRP3 levels were detected in 65.8% of patients and correlated significantly with HHV-6 antigen presence, particularly in hematological and genitourinary cancers. Viral antigenemia and inflammasome activity were more prominent in females and older patients. Host gene analysis revealed Hepcidin (HAMP) polymorphisms and altered expression compared to healthy controls, suggesting links between iron metabolism, viral antigenemia, and inflammasome activity. These findings highlight a potential mechanistic connection between HHV-6 antigenemia and inflammasome-driven inflammation, which may contribute to chemotherapy-associated immune dysregulation. Monitoring HHV-6 antigenemia and NLRP3 activation may offer valuable insight into the inflammatory status of cancer patients undergoing chemotherapy. Full article

Background/Objectives: Since 2023, a significant increase in measles cases has been reported worldwide, and Italy has been among the most affected European countries. In this context, the integration of laboratory and epidemiological data enables timely case classification and helps distinguish between imported and indigenous cases, supporting disease control. However, most studies address only selected aspects of surveillance. Therefore, this study aimed to provide an integrated analysis of virological and epidemiological surveillance activities conducted between November 2023 and December 2025 by the Regional Reference Laboratory in the Emilia-Romagna Region (ERR). Methods: A total of 806 clinical samples (269 urine, 267 oral fluids—saliva or oropharyngeal swabs—and 270 sera) from 291 suspected measles cases were tested by molecular and/or serological methods, and MV genotyping was performed. Samples from discarded cases were also analysed for parvovirus B19 (B19V), human herpesvirus 6 (HHV-6), enterovirus (EV), and varicella zoster virus (VZV), chikungunya virus (CHIKV) and dengue virus (DENV). Results: Of 291 suspected cases, 176 (60.5%) were confirmed. Median age was 33 years, with 46% in the 15–39 year group. Vaccination status was available for 165: 90.3% were unvaccinated, 5.4% had one dose, and 4.2% had two doses. Notably, over half of confirmed cases occurred in areas with vaccine-hesitant communities. MV strain characterisation was performed in 99.4% of MV-RNA positive cases, with 84.3% genotype D8 and 15.6% genotype B3; 83% of strains were of indigenous origin, suggesting an ongoing endemic circulation. Clinical data showed complications in 19.3%, mainly pneumonia and diarrhoea. Additionally, differential diagnosis enabled the identification of the etiological agent in 37.5% of measles/rubella discarded cases, and 37.6% (29/77) tested positive for B19V. Conclusions: The study results highlight that effective measles surveillance must be supported by integrating timely virological diagnosis, molecular and epidemiological investigations, and differential diagnosis, to achieve the WHO goals of eliminating measles transmission. Full article

Background/Objectives: Miller–Fisher syndrome (MFS) is a rare Guillain–Barré variant defined by ophthalmoplegia, ataxia, and areflexia. Pediatric MFS is uncommon, and infectious triggers remain underrecognized. Human herpesvirus 6 (HHV-6) is neurotropic but rarely linked to immune-mediated neuropathies. In this paper, we describe a child with MFS associated with HHV-6 detected in cerebrospinal fluid (CSF) and review reported pediatric infections related to MFS. Methods: A 5-year-old girl presented with acute ophthalmoplegia, ataxia, and diminished reflexes. Neuroimaging, ophthalmologic tests, CSF analyses, and serologic andpolymerase chain reaction (PCR) assays were performed, including multiplex reverse transcription–PCR of cerebrospinal fluid using the BioFire^® Meningitis/Encephalitis panel. A literature search was performed on Pubmed to identify pediatric (0–18 years) MFS cases with infectious triggers. Two reviewers independently screened and summarized the literature, and a PRISMA-style flow diagram was used to transparently report the study selection process. Results: HHV-6 DNA was detected via CSF PCR twice, while tests for other pathogens were negative. Anti-GQ1b and related antibodies were negative or borderline. The patient received intravenous immunoglobulin and corticosteroids, with full recovery after one month. Among 20 published pediatric cases (1997–2021), Campylobacter jejuni was most frequent, followed by Mycoplasma pneumoniae and influenza viruses. Anti-GQ1b IgM positivity and favorable outcomes were commonly reported, including cases managed conservatively. Conclusions: This case raises the hypothesis that HHV-6 may represent a potential post-infectious association in pediatric MFS. The review findings indicate that pediatric MFS generally follows infection, responds well to immunotherapy, and has an excellent prognosis. Viral testing may be considered in selected, hypothesis-generating contexts in atypical or seronegative pediatric MFS presentations. Full article

The U94 protein of Human Herpesvirus 6 exerts antiproliferative effects through downregulation of the Src proto-oncogene. We aimed to define the shortest U94 fragment that preserves antiproliferative activity and to explore its structural properties. U94 was truncated into shorter fragments, which were subjected to computational analyses and proliferation assays on MDA-MB-468, BT-549 breast cancer cells. Src phosphorylation levels were scrutinized by Western blot analysis. Data obtained demonstrated that the U94 antiproliferative activity resides in its N-terminal region. Specifically, MT153 (aa 1–153) and MT117 (aa 1–117) fragments exhibited antiproliferative activity, whereas MV85 (aa 1–85) fragment did not. Computational analyses identified MG112 (aa 1–112) and MI108 (aa 1–108) as biologically active and suggested that the β-sheet of the structure is critical. The shortest KI95 fragment (aa 14–108), maintaining a stable β-sheet, demonstrated antiproliferative effects and Src downregulation. The antiproliferative activity of U94 and its active fragments relies on stable tridimensional conformation rather than on linear peptide sequence. KI95 represents the shortest active U94 fragment that preserves biological function, with critical residues likely located within the β-sheet region. These findings highlight the importance of structural integrity in U94 functionality and suggest KI95 as a potential therapeutic agent for cancer treatment. Full article

Natural killer (NK) cells are central to antiviral immunity through a balance of activating and inhibitory receptors, including killer immunoglobulin-like receptors (KIRs). We have previously observed that an increased frequency of the inhibitory receptor KIR2DL2 and its ligand HLA-C1 is associated with heightened susceptibility to human herpesvirus (HHV) infection, supporting a role for KIR-mediated NK cell regulation in host–virus interactions. We investigated whether the co-infection of SARS-CoV-2 and human herpesvirus 6 (HHV-6) might be connected to the expression of KIR2DL2/HLA-C1. We analyzed 110 SARS-CoV-2-positive subjects and 109 SARS-CoV-2-negative subjects for the KIR2DL2 and HLA-C1 genotype and for HHV-6A/B reactivation in plasma samples. SARS-CoV-2-positive subjects showed a significantly higher frequency of the KIR2DL2/HLA-C1 haplotype and increased reactivation of HHV-6A. Among deceased and comorbid patients, the co-occurrence of the KIR2DL2/HLA-C1 haplotype and HHV-6A DNAemia was more frequent, particularly in those with cardiovascular disorders. These findings suggest that the KIR2DL2/HLA-C1 haplotype might promote NK cell inhibition, facilitating HHV-6A persistence and contributing to immune dysregulation during SARS-CoV-2 infection. The combined presence of KIR2DL2/HLA-C1 and HHV-6A may, therefore, represent a molecular signature of COVID-19 outcomes. Full article

Background/Objectives: Polymerase chain reaction (PCR) testing of ocular fluids is an essential diagnostic method for identifying infectious causes of uveitis. However, multiplex PCR kits specifically developed for ophthalmic use are not commercially available in many regions, including Korea. Given the biochemical similarity between cerebrospinal fluid (CSF) and aqueous humor, this study evaluated the diagnostic utility of a commercially available CSF multiplex PCR panel for detecting herpesviruses in patients with suspected viral uveitis. Methods: We retrospectively reviewed the medical records of patients whose aqueous humor samples were analyzed using a multiplex PCR assay originally designed for CSF testing (Seeplex Meningitis-V1 ACE Detection kit, Seegene, Seoul, Republic of Korea). The samples were obtained between May 2019 and June 2023 at two tertiary referral hospitals. The assay targeted herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and human herpesvirus 6 (HHV-6). Patients were classified into three groups: (I) anterior uveitis with suspected herpesviral infection, (II) acute retinal necrosis (ARN), and (III) CMV retinitis. Baseline characteristics, PCR positivity rates, and virus prevalence were compared among the groups. Results: Among 149 eyes tested, 86 were included in the final analysis. The overall positivity rate was 38.4%. PCR positivity was 19.7% (12/61) in Group I, 93.8% (15/16) in Group II, and 66.7% (6/9) in Group III. CMV was the most common pathogen in Groups I (66.7%) and III (100%), while VZV was predominant in Group II (80%). No HHV-6 infection was detected. Conclusions: The positivity rate in anterior uveitis (Group I) was lower than previously reported, likely due to the limited sample volume relative to the assay’s requirement. Nevertheless, the assay demonstrated diagnostic reliability comparable to previous reports for ARN and CMV retinitis. Therefore, the CSF-based multiplex PCR panel serves as a feasible and cost-effective diagnostic option for sight-threatening posterior segment infections, facilitating prompt diagnosis and treatment, although further optimization is warranted for anterior uveitis. Full article

Human herpesvirus 6 (HHV-6) is a common virus that can reactivate in immunocompromised patients, including lung transplant (LT) recipients. This study aimed to evaluate the clinical and functional implications of HHV-6 infection in LT patients through a retrospective analysis of 175 individuals who underwent lung transplantation at the City of Health and Sciences of Turin between 2014 and 2023. Surveillance bronchoscopies—including bronchoalveolar lavage (BAL) and transbronchial biopsies—were performed at scheduled intervals over a two-year period to detect HHV-6 and other pathogens, and to assess acute rejection. Spirometries were performed to evaluate graft function. Among the cohort, 33% of 822 BAL samples tested were positive for HHV-6, with a notable association between high viral load (≥500 copies/mL) and the development of post-transplant lymphoproliferative disorder (PTLD) (13% vs. 1%, p = 0.02) at 1 month and (9% vs. 1%, p = 0.026) at 12 months. Co-infection with CMV (78% in positives vs. 55% in negatives; p = 0.006), Epstein–Barr virus (EBV) (35% vs. 16%; p = 0.010), and bacterial and fungal infection (specifically, a higher rate of isolation of Achromobacter xylosoxidans (13%), p = 0.010) was frequently observed in conjunction with HHV-6 positivity. Notably, patients with at least one HHV-6 positive BAL exhibited a significant reduction in forced vital capacity (FVC) at multiple follow-up points, FVC 82% in positives vs. 92% in negatives (p = 0.038) at 4 months and 87% vs. 98% p = 0.033 at 8 months and 87% vs. 99% p = 0.038 at 24 months. No direct associations with acute rejection or overall survival were found. By means of this study, we provide a wide overview of HHV-6 in lung transplant recipients, filling in a gap of evidence in the field. We report a remarkable incidence and a significant association with acknowledged clinically relevant viral infections, PTLD, and functional tests decline, with no association with mortality. Full article

Background/Objectives: Central nervous system (CNS) infections remain a significant public health challenge and require rapid and accurate diagnosis to guide clinical management. Although the incidence of bacterial meningitis has declined owing to widespread vaccination, viral etiologies continue to dominate CNS infections. The aim of this study was to assess the epidemiological trends, age distribution, and seasonality of CNS infections using multiplex PCR. Methods: A retrospective analysis was conducted on cerebrospinal fluid (CSF) samples collected between January 2021 and December 2022 from patients with CNS infections at King Abdulaziz Medical City. A BioFire FilmArray Meningitis/Encephalitis (ME) panel was used to detect pathogens. Patient demographics, pathogen distribution, and seasonal trends were analyzed. Results: A total of 2460 CSF samples were tested, of which 130 (5%) were positive for at least one pathogen. Viral pathogens accounted for 82.3% of the infections, with human herpesvirus-6 (HHV-6) (31%) and enterovirus (EV) (20%) being the most common. Bacterial pathogens represented 17.7% of the cases, with Streptococcus pneumoniae (6%) and Escherichia coli K1 (5%) being the predominant bacterial agents. The highest infection burden was observed in infants aged 0–6 months, with a marked male predominance. Seasonal analysis revealed multiple peaks in viral infections, particularly of HHV-6 and EVs, whereas bacterial infections were sporadic, with Streptococcus agalactiae and Streptococcus pneumoniae peaking in October and November. Conclusions: Viral infections, particularly HHV-6 and EVs, dominated CNS infections, with distinct seasonal and age-related variations. These findings underscore the value of multiplex PCR in improving the rapid diagnosis of CNS infections and aiding in timely treatment and antimicrobial stewardship. Full article

Human herpesvirus 6 (HHV-6) establishes lifelong latency in immune cells and may contribute to the progression of ethanol-induced liver injury. To elucidate the contribution of HHV-6 to alcohol-induced hepatic injury, this study evaluated HHV-6 protein expression, NF-κB signalling, and CD163-positive macrophage recruitment in liver samples from control subjects, young individuals with recent alcohol exposure, and individuals with long-term chronic alcohol use. Liver lobules displaying HHV-6 positivity were more frequent in alcohol users (64% in young and 72% in chronic users) compared to controls (48%). CD163-positive macrophage counts were higher in both young and chronic alcohol users compared to controls, with the greatest increase in HHV-6-positive chronic users. NF-κB expression intensity was elevated in alcohol users (p < 0.005), and further increased in HHV-6-positive samples (p = 0.02). These findings indicate an association between HHV-6 persistence, NF-κB pathway activation, and CD163-positive macrophage-driven inflammatory responses in liver tissue under conditions of chronic alcohol use. Further research is warranted to uncover the mechanisms underlying the interaction between HHV-6 and ethanol in liver injury. Full article

Bacterial meningitis is one of the most serious infections. Salmonella meningitis is associated with a high prevalence of long-term adverse outcomes, often linked to acute complications and a broad range of potential neurological sequelae following the infection. Acute complications such as brain abscesses and chronic complications such as hearing loss and developmental delay. In this report, we present a case of a 2-month-old male patient with seizures, hypoactivity and respiratory symptoms, who was found to have Salmonella bacteremia complicated by Salmonella and Human Herpes Virus-6 (HHV-6) meningitis, as well as rhinovirus bronchiolitis, along with follow-up findings. The patient’s data, including demographics, presenting symptoms, physical examination findings, and whole exome sequence results, as well as investigations such as complete blood count (CBC), cerebrospinal fluid (CSF) analysis, liver enzyme levels, and imaging findings, were collected from the electronic medical record system using a case report form. In addition, immunological workups were performed, as serious Salmonella infections were more common in immunocompromised patients. In the literature, there was no clear correlation between Salmonella and HHV-6 meningitis, rhinovirus bronchiolitis, and the complications that developed in this infant. This case report provides valuable insights into the clinical spectrum and long-term outcomes of patients with Salmonella meningitis. Full article

Co-infection of Orientia tsutsugamushi and influenza A virus complicates diagnosis and treatment in endemic regions because of overlapping clinical features and potential synergistic inflammation. We describe a 68-year-old woman from Hainan, China, who presented with five days of high fever (39.2 °C), nonproductive cough, eschar formation, lymphadenopathy, cytopenias, elevated liver enzymes, and raised inflammatory markers. On the day of admission, influenza A was confirmed by rapid antigen test and Orientia tsutsugamushi IgM/IgG was detected via colloidal-gold immunochromatography, prompting concurrent oseltamivir and doxycycline therapy. Quantitative PCR on day 2 measured an Orientia tsutsugamushi load of 2.85 × 10⁴ copies/mL (Cq 28.86), and targeted next-generation sequencing on day 3 revealed a high H1N1pdm09 viral burden (>1 × 10⁶ copies/mL) with low-level human herpesvirus 1 co-detection. Nested PCR and Sanger sequencing assigned Orientia tsutsugamushi to the Karp_A lineage and influenza A to clade 6B.1A.5a.2a. The patient defervesced by hospital day 2, laboratory indices normalized by day 3, and radiographic abnormalities resolved by day 6. This first documented Orientia tsutsugamushi–influenza A co-infection in China highlights the value of integrating rapid serology, qPCR quantification, nested PCR genotyping, and tNGS for early, precise dual-pathogen identification. Systematic multi-pathogen screening during overlapping transmission seasons is recommended to guide timely combination therapy and enhance epidemiological surveillance. Full article